A Randomized, Double Blind, Placebo-controlled, Multi-center, Parallel Group Study to Evaluate the Efficacy and Safety of Dupilumab in Patients With Prurigo Nodularis Who Are Inadequately Controlled on Topical Prescription Therapies or When Those Therapies Are Not Advisable
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 151
- 试验地点
- 63
- 主要终点
- Percentage of Participants With Improvement (Reduction) in Worst Itch Numeric Rating Scale (WI-NRS) Scores by Greater Than or Equal to (>=) 4 Points From Baseline to Week 24
研究概览
简要总结
Primary Objective:
To demonstrate the efficacy of dupilumab on itch response in participants with prurigo nodularis (PN), inadequately controlled on topical prescription therapies or when those therapies are not advisable.
Secondary Objectives:
To demonstrate the efficacy of dupilumab on additional itch endpoints in participants with PN, inadequately controlled on topical prescription therapies or when those therapies are not advisable.
To demonstrate efficacy of dupilumab on skin lesions of PN. To demonstrate the improvement in health-related quality of life. To evaluate safety outcome measures. To evaluate immunogenicity of dupilumab.
详细描述
The duration of study for each participant included 2-4 weeks of screening period, 24 weeks of treatment period and 12 weeks of post treatment period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must be 18 to 80 years of age, at the time of signing the informed consent.
- •With a clinical diagnosis of PN defined by all of the following:
- •Diagnosed by a dermatologist for at least 3 months before the screening visit.
- •On the worst-Itch Numeric Rating Scale (WI-NRS) ranged from 0 to 10, participants who had an average worst itch score of greater than or equal to (>=) 7 in the 7 days prior to Day
- •Participants who had a minimum of 20 PN lesions in total on both legs, and/or both arms and/or trunk, at screening visit and Day
- •History of failing a 2-week course of medium-to-superpotent TCS or when TCS were not medically advisable.
- •Had applied a stable dose of topical emollient (moisturizer) once or twice daily for at least 5 out of the 7 consecutive days immediately before Day
- •Was willing and abled to complete a daily symptom electronic-diary for the duration of the study.
排除标准
- •Participants were excluded from the study if any of the following criteria apply:
- •Presence of skin morbidities other than PN and mild atopic dermatitis (AD) that interfered with the assessment of the study outcomes.
- •PN secondary to medications.
- •PN secondary to medical conditions such as neuropathy or psychiatric disease.
- •Within 6 months before the screening visit, or documented diagnosis of moderate to severe AD from screening visit to randomization visit.
- •Severe concomitant illness(es) under poor control that, in the investigator's judgment, would adversely affect the participant's participation in the study.
- •Severe renal conditions (eg, participants with uremia and/or on dialysis).
- •Participants with uncontrolled thyroid disease.
- •Active tuberculosis or non-tuberculous mycobacterial infection, or a history of incompletely treated tuberculosis unless documented adequately treated.
- •Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection, unless clinical and (if necessary) laboratory assessment had ruled out active infection before randomization.
- •Active chronic or acute infection (except human immunodeficiency virus infection) required treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before the screening visit or during the screening period.
- •Known or suspected immunodeficiency.
- •Active malignancy or history of malignancy within 5 years before the baseline visit, except completely treated in situ carcinoma of the cervix, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin.
- •The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
研究组 & 干预措施
Dupilumab
Participants received dupilumab at a loading dose of 600 milligrams (mg), subcutaneously (SC) on Day 1 followed by dupilumab 300 mg once every 2 weeks (q2w) for 24 weeks added to background therapy of topical corticosteroids/topical calcineurin inhibitors (TCS/TCI) at stable dose.
干预措施: Dupilumab SAR231893 (Drug)
Dupilumab
Participants received dupilumab at a loading dose of 600 milligrams (mg), subcutaneously (SC) on Day 1 followed by dupilumab 300 mg once every 2 weeks (q2w) for 24 weeks added to background therapy of topical corticosteroids/topical calcineurin inhibitors (TCS/TCI) at stable dose.
干预措施: Moisturizers (Drug)
Dupilumab
Participants received dupilumab at a loading dose of 600 milligrams (mg), subcutaneously (SC) on Day 1 followed by dupilumab 300 mg once every 2 weeks (q2w) for 24 weeks added to background therapy of topical corticosteroids/topical calcineurin inhibitors (TCS/TCI) at stable dose.
干预措施: Low to medium potent topical corticosteroids (Drug)
Dupilumab
Participants received dupilumab at a loading dose of 600 milligrams (mg), subcutaneously (SC) on Day 1 followed by dupilumab 300 mg once every 2 weeks (q2w) for 24 weeks added to background therapy of topical corticosteroids/topical calcineurin inhibitors (TCS/TCI) at stable dose.
干预措施: Topical calcineurin inhibitors (Drug)
Placebo
Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose.
干预措施: Placebo (Drug)
Placebo
Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose.
干预措施: Moisturizers (Drug)
Placebo
Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose.
干预措施: Low to medium potent topical corticosteroids (Drug)
Placebo
Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose.
干预措施: Topical calcineurin inhibitors (Drug)
结局指标
主要结局
Percentage of Participants With Improvement (Reduction) in Worst Itch Numeric Rating Scale (WI-NRS) Scores by Greater Than or Equal to (>=) 4 Points From Baseline to Week 24
时间窗: Baseline, Week 24
WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Percentage of participants with improvement (reduction) in WI-NRS scores by \>=4 points from Baseline to Week 24 is reported in this outcome measure.
次要结局
- Percentage of Participants With Both an Improvement (Reduction) in WI-NRS Scores by >=4 Points and an IGA PN-S Scores of 0 or 1 From Baseline at Week 24(Baseline, Week 24)
- Change From Baseline in Skin Pain-NRS at Week 24(Baseline, Week 24)
- Percent Change From Baseline in WI-NRS Scores at Week 24(Baseline, Week 24)
- Percentage of Participants With Investigator's Global Assessment For Prurigo Nodularis-Stage (IGA PN-S) Scores of 0 or 1 at Week 24(At Week 24)
- Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) at Week 24(Baseline, Week 24)
- Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Total Score at Week 24(Baseline, Week 24)
- Probability of Participants With an Improvement (Reduction) in WI-NRS Scores by >=4 Points From Baseline at Week 24(Baseline, Week 24)
- Change From Baseline in WI-NRS Scores at Week 12 and 24(Baseline, Weeks 12 and 24)
- Percent Change From Baseline in WI-NRS Scores at Weeks 2, 4 and 12(Baseline, Weeks 2, 4 and 12)
- Percent Change From Baseline in WI-NRS Scores at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24(Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24)
- Percentage of Participants With Improvement (Reduction) in WI-NRS Scores by >=4 Points From Baseline at Week 12(Baseline, Week 12)
- Percentage of Participants With Improvement (Reduction) in WI-NRS Scores by >=4 Points From Baseline at Week 4(Baseline, Week 4)
- Percentage of Participants With Investigator's Global Assessment for PN-Stage (IGA PN-S) 0 or 1 Score at Weeks 4, 8, and 12(At Weeks 4, 8 and 12)
- Percentage of Participants Achieving >=4 Points Improvement (Reduction) From Baseline in WI-NRS Scores at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24(Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24)
- Percentage of Participants With Investigator's Global Assessment for PN-Activity (IGA PN-A) 0 or 1 Score at Weeks 4, 8, 12 and 24(At Weeks 4, 8, 12 and 24)
- Number of Participants With Treatment-emergent and Treatment Boosted Antidrug Antibodies (ADA)(From the first IMP administration to the last IMP administration + 14 weeks (i.e., up to 36 weeks))
- Onset of Action Based on Change From Baseline in WI-NRS Scores at Week 3(Baseline, Week 3)
- Change From Baseline in IGA PN-S Scores at Weeks 4, 8, 12, and 24(Baseline, Weeks 4, 8, 12, and 24)
- Change From Baseline in HRQoL as Measured by DLQI at Week 12(Baseline, Week 12)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)(From the first IMP administration to the last IMP administration + 14 weeks (i.e., up to 36 weeks))